Alterations of overused supraspinatus tendon: A possible role of glycosaminoglycans and HARP/pleiotrophin in early tendon pathology
Alterations of overused supraspinatus tendon: A possible role of glycosaminoglycans and HARP/pleiotrophin in early tendon pathology
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DOI：
10.1002/jor.21479
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发表时间：
2012-01-01
影响因子：
2.8
通讯作者：
Martelly, Isabelle
中科院分区：
文献类型：
--
作者：
Attia, Mohamed;Scott, Alexander;Martelly, Isabelle
冈上肌腱过度使用损伤会导致运动员和工人严重疼痛和残疾。尽管这些伤害很普遍且社会成本很高，但早期的病理事件尚不清楚。我们使用肩袖过度使用的大鼠模型分析了糖胺聚糖 (GAG) 组成与表型细胞改变之间的潜在关系。过度使用 4 周后，硫酸化 GAG 总量增加，并在 16 周内保持较高水平。两周后，核心蛋白聚糖、多功能蛋白聚糖和聚蛋白多糖 (PG) mRNA 和蛋白质以及双糖链蛋白聚糖 PG mRNA 上调，随后 GAG 积累。 2 周时，胶原蛋白 1 转录物减少，而胶原蛋白 2、胶原蛋白 3、胶原蛋白 6 和转录因子 Sox9 的 mRNA 增加。肝素亲和调节肽 (HARP)/多效素（一种已知调节发育软骨细胞形成的细胞因子）的蛋白质水平尤其在 4 周时增强，而 HARP/多效素 mRNA 没有上调。进一步的结果表明，早期病变中存在的 GAG 增加可能会隔离 HARP/多效蛋白，这可能导致肌腱细胞表型的丧失。所有这些修饰都是向软骨细胞表型转变的特征。识别细胞外基质的这些早期变化可能有助于防止病理进展为更加致残的退行性改变。 (c) 2011 年骨科研究协会，Wiley periodicals, Inc. 出版。J Orthop Res 30:6171, 2012
Supraspinatus tendon overuse injuries lead to significant pain and disability in athletes and workers. Despite the prevalence and high social cost of these injuries, the early pathological events are not well known. We analyzed the potential relation between glycosaminoglycan (GAG) composition and phenotypic cellular alteration using a rat model of rotator cuff overuse. Total sulfated GAGs increased after 4 weeks of overuse and remained elevated up to 16 weeks. GAG accumulation was preceded by up-regulation of decorin, versican, and aggrecan proteoglycans (PGs) mRNAs and proteins and biglycan PG mRNA after 2 weeks. At 2 weeks, collagen 1 transcript decreased whereas mRNAs for collagen 2, collagen 3, collagen 6, and the transcription factor Sox9 were increased. Protein levels of heparin affine regulatory peptide (HARP)/pleiotrophin, a cytokine known to regulate developmental chondrocyte formation, were enhanced especially at 4 weeks, without up-regulation of HARP/pleiotrophin mRNA. Further results suggest that the increased GAGs present in early lesions may sequester HARP/pleiotrophin, which could contribute to a loss of tenocyte's phenotype. All these modifications are characteristic of a shift towards the chondrocyte phenotype. Identification of these early changes in the extra-cellular matrix may help to prevent the progression of the pathology to more disabling, degenerative alterations. (c) 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 30:6171, 2012